The present invention relates to processes for generating boron-containing compounds and bi-aryls.
The Suzuki-type coupling to form bi-aryl compounds is usually accomplished by reacting boronic acids with aryl moieties having leaving groups such as halogen, triflates, and diazonium salts, among others.
In a typical Suzuki coupling, a N-t-butoxycarbonyl-substituted pyrrole (N-Boc-pyrrole) is first deprotonated using butyllithium compounds. The lithiated N-Boc-pyrrole is then quenched with a trialkylborate, typically triisopropyl borate, and the intermediate reacted with a bromoaryl compound in the presence of a palladium catalyst to couple the aryl and pyrrole moieties. Subsequent cyanation of the pyrrole moiety followed by Boc deprotection and N-methylation gives the coupled product.
This lengthy coupling is plagued by non-selective methylation of the cyano substituent. Further, the intermediates generated during the coupling have been reported to be thermally unstable.
What is needed in the art are alternative methods for coupling aryl compounds.